ABSTRACT
IntroductionIntradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy due to systemic reactogenicity among older adults. ObjectivesTo compare the immunogenicity and reactogenicity of fractional ID and standard intramuscular (IM) booster vaccination of mRNA-1273 and BNT162b2 vaccines in older adults. MethodsParticipants aged [≥]65 years who previously vaccinated with 2-dose ChAdOx1 were randomized to receive one of the four booster vaccinations: 0.1mL ID mRNA-1273, 0.5mL IM mRNA-1273, 0.1mL ID BNT162b2 and 0.3mL IM BNT162b2. Immunogenicity as measured by anti-receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NAb) against Wuhan and Omicron BA.1, BA.2 and BA.4/5, and IFN{gamma}-producing cells. Local and systemic adverse effects (AEs) were self-reported via an electronic diary card. ResultsOf the 210 participants enrolled, 70.5% were female and median age was 77.5 years (interquartile range (IQR): 71.0-84.0). Following the booster dose, both ID vaccination induced 37% lower levels of anti-RBD IgG than IM vaccination of the same vaccine. NAb against ancestral and Omicron BA.1 strains was highest following IM mRNA-1273 (1,718 and 617), followed by ID mRNA-1273 (1,212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN{gamma} responses were similar or higher in the ID groups when compared with their respective IM groups. Vaccine delivery through ID route tended to have lower systemic AEs, although more local AEs reported in ID mRNA-1273 group. ConclusionsFractional ID vaccination induced immunogenicity and reactogenicity comparable to IM and may be an alternative option for older people. Key pointsO_LIFractional dose intradermal mRNA COVID-19 booster vaccination induces robust immunogenicity in adults aged [≥]65 years. C_LIO_LIFor each vaccine, intradermal route induced lower humoral but similar or higher cellular immune responses than IM route. C_LIO_LIIntradermal mRNA-1273 vaccination induced similar immunogenicity to intramuscular BNT162b2 vaccination. C_LIO_LIImmune responses were marginally lower among participants aged [≥]80 years than among participants aged 65-79 years. C_LIO_LISystemic reaction was lower following intradermal mRNA COVID-19 vaccination compared with intramuscular vaccination. C_LI
